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EATING BEHAVIOUR IN PHYSIOLOGICAL AND
PATHOLOGICAL AGING
E. Ferrari
Dept of Internal Medicine and Medical Therapy, Chair of Gerontology and
Geriatrics – University of Pavia, Italy
Morgan Hall, Room 114– University of California, Berkeley
Thursday May 5, 2005
signals
IDENTIFICATION
sensory
aspect
pleasure
HEDONICS
source of
feels
NUTRITION
FOOD
(Blundell - Münich 1995)
Biological
regulation
Brain
Eating
behaviour
Physiology
Metabolism
Nutrition
Enviromental
adaptation
(BLUNDELL J.E. et HILL A.- PV 1992)
FACTORS INVOLVED IN THE REGULATION OF
EATING BEHAVIOUR
Internal signals
Environmental changes
Metabolic
(glucose-lipids
amino acids)
Hormonals
(insulin
Gastrointestinal hormones)
Food
palatability
HYPOTHALAMUS
Neurogens
(gastric distension)
Eating behaviour
Thermostatic
Hungry - satiety
Adversive behaviours
about food
Psychological cortical
factors
EATING BEHAVIOUR
AREAS INVOLVED
MAINTENANCE OF
BODY WEIGHT
• Long term signals
• Fat mass
• nutrients
• hormones
SHORT TERM MECHANISMS
(hungry/satiety feeling)
• Gastrointestinal pathway
(neuronal/hormonal messages)
• Pancreatic hormones
• Nutrients
• taste
• memory
• environmental factors
•
•
•
•
•
food research
food choice
food intake
thermogenesys
Other metabolic
factors
HYPOTHALAMUS
LATERAL AREA
(Dopamine)
HUNGER
VENTROMEDIAL AREA
(Serotonin)
SATIETY
MAIN FACTORS INVOLVED IN THE REGULATION OF
FOOD INTAKE
STIMULATORS
INHIBITORS
Neuropeptide Y (NPY)
Serotonin
Glucocorticoids
Leptin
Opioids
Insulin (central)
GABA
CRF
Galanin
Cholecystokinine (CCK)
Noradrenalin
Bombesin
PYY
Catecholamines
PP
Somatostatin
AGE-RELATED CHANGES OF THE MAIN FACTORS INVOLVED IN
THE CONTROL OF EATING BEHAVIOUR AND THEIR
CONSEQUENCES
Factors
Age
Consequences
Opioids
Reduction of caloric uptake (particularly fats)
CCK
Early satiety sensation
Nitric oxide
Early satiety sensation
Cytokines (TNFa)
Increased protein catabolism, lipolysis
Amilyn
Reduction of protein anabolism (insulin antagonism)
Taste and smell
Reduction of caloric uptake
GH / IGF-1
Reduction of caloric uptake, lowering of protein anabolism
Testosterone
Reduction of caloric uptake, lowering of protein anabolism
Estrogens
Reduction of caloric uptake
GERONT.GERIATR., PAVIA
Effect of aging on BMI, body fat and muscle mass
in men and women
(BLSA, cross sectional analysis)
60
% difference
40
Men
% fat
Women
% fat
20
BMI
BMI
0
-20
muscle
mass
-40
muscle
mass
-60
30
40
50
60
70
80
90
30
40
50
60
70
80
90
Age(years)
Muller et al, 1994
CALORIC REQUIREMENT AND ENERGY
EXPENDITURE ACCORDING TO AGE
(Baltimore Longitudinal Study)
 Daily caloric requirement :
30 y = 2700 Kcal
80 y = 2100 Kcal
 Reduction of metabolic basal rate:
- 1.66 Kcal / m 2 / h /10 y
 Reduction of energy expenditure during
physical activity :
- 200 Kcal/die from 45 to 75 y
- 500 Kcal/die after 75 y
GERONT.GERIATR., PV,
FOOD
INTAKE
ENERGY
EXPENDITURE
WEIGHT LOSS:
FOOD INTAKE
ENERGY EXPENDITURE
FOOD INTAKE
ENERGY EXPENDITURE
FOOD INTAKE
ENERGY EXPENDITURE
HYPOTHALAMUS
PERIPHERY
from Jeanrenaud, PD 1997
LEPTIN
• Polypeptide hormone secreted by fat cells
• Blood levels proportional to total fat mass
• Plasma circadian rhythm: acrophase during the
night (4 am), nadir during the afternoon
• Pulsatility in opposite phase with ACTH and
cortisol
• Effects: - appetite inhibition
- effects on GH-RH and GnRH
INTERACTION LEPTIN - NPY
Hypothalamic NPY
food intake
BAT activity
insulin secretion
LEPTIN
FAT MASS
Long-term regulation: LEPTIN
Decrease of food
intake
LEPTIN
Increase of energy
expenditure
(sympathetic
activation)
WEIGHT
LOSS
The biological impact of leptin is probably more
pronounced when leptin levels are decreasing.
Increased sensation of hunger correlated with reduction
of plasma levels during moderate energy restriction
Short-term regulation: LEPTIN
Stomach is a source of leptin
Food or CCK administration
induces leptin secretion
Enhanced effect of gastrointestinal
satiety factors in the presence of
leptin
Bado A, et al, Nature, 1998; Cinti S et al, Int J Obes, 2000
Cholecystokinine (CCK)
Endocrine cells of the proximal small intestine
Stimulated by dietary fats, amino acids and small
peptides
Inhibition of food intake by activation of CCKA
receptors (vagal afferent signals)
Decrease of meal size
Inhibition of gastric emptying
Cholecystokinine (CCK)
In the CNS, CCK is released from hypothalamic
neurons during feeding
ICV administration (very low doses) inhibits food
intake (CCKA)
Leptin/CCK synergy
might promote weight
loss through:
 resting metabolic
rate
 thermogenesys
 efficiency of
absorption and
storage of nutrients
Matson CA et al, 2000
GHRELIN
Produced by stomach and hypothalamus
 during fasting and  by the presence of
nutrients in the stomach
Central administration
expression of NPY
increases
hypothalamic
Potential role in long-term body weight regulation
(increase of adiposity sustained over 1 week of
treatment)
GHRELIN
Wren MA et al, 2001
Intraperitoneal injection
Central injection
GHRELIN : orexigenic effects
Increase of food intake independently from GH and
GHRH release
The increased expression of hypothalamic NPY
mRNA is abolished by co-injection of Y1 receptor
antagonist
The satiety effect of leptin is abolished by coinjection of ghrelin  leptin / ghrelin antagonism
(NPY/Y1 pathway)
Orexigenic effect mediated partly by increases of
AgRP production, leading to the inhibition of
hypothalamic melanocortin system
CYTOKINES
IL-6, TNF-α = physiological regulators ?
They may influence insulin sensitivity or
leptin production
GLUCOCORTICOIDS
CATABOLIC in periphery
ANABOLIC in the CNS
Interaction with insulin and leptin in long-term regulation
of food intake and adiposity
Long-term regulation: INSULIN
Food intake
+
Insulin
Parasimpathetic nerves
Incoming nutrients (glucose and
aminoacids)
Incretin hormones (GLP-1 and GIP)
Insulin concentration proportional to body fat
content and recent carbohydrate and protein intake
Long-term regulation: INSULIN
 THERMOGENESYS
 FOOD INTAKE
CNS
NPY, melanocortin system
Sympathetic
activity
Food intake
+
Insulin
Long-term regulation: INSULIN
Peripheral anabolic effects (Increased lipid synthesis
and storage)
Insulin response to glucose = smaller degree of
subsequent weight gain
Post feeding insulin preferentially transported into
the hypothalamus
Chronic consumption of high fat diet impairs brain
insulin transport
MCH = melanin concentrating
hormone
NPY = neuropeptide Y
CRF = corticotropin-releasing
factor
AGRP = agoute-related peptide
CART = cocaine-amphetamineregulated transcript
CCK = cholecystokinin
GLP-1= glucagon-like
peptide-1
GRP= gastric-related peptide
PYY = peptide YY
TNF = tumor necrosis factor
IL = interleukin
NO = nitric oxide
From MORLEY J.E., J Geront Med Sci, 58A, 2, 131-137, 2003
BMI acceptable values
(National Academy Press, Washington, DC, 1989, pp 21-22)
45 - 54 y
More than 65 y
21 – 26 Kg/m2
24 – 29 Kg/m2
ANOREXIA:
“LOSS OF THE DESIRE TO EAT”
ANOREXIA OF ELDERLY SUBJECTS
1. SINE CAUSA
2. DEPRESSION
3. SENILE AND PRESENILE DEMENTIA
OF ALZHEIMER’S TYPE
4. ATYPICAL ANOREXIA NERVOSA
“PHYSIOLOGICAL ANOREXIA” OF AGING
Basal Metabolic Rate
Physical Activity
Feeding drive (NE, NPY, dynorphin)
CCK
NO
(From MORLEY - Am. J. Clin. Nutr. 66: 760: 1997)
GERONT. GERIATR., PAVIA
 GH, DHEA, T, E
 Free Radicals
 Cytokines
 Activity
 Chronic Disease
 Acute illness
 Cytokines
 Activity
Ageing
Wt Loss
? Wt Loss
FTT
Sarcopenia
Frailty
Proposed interrelationships between weight loss (Wt Loss), sarcopenia,
failure to thrive (FTT), and frailty. GH, growth hormone; DHEA,
dehydroepiandrosterone sulfate; T, testosterone; E, estrogen.
“STANDARDIZATION OF NOMENCLATURE OF
BODY COMPOSITION IN WEIGHT LOSS”
WASTING: involuntary weight loss with loss of both
lean and the fat mass
CACHEXIA: involuntary loss of BCM (Body Cell
Mass) of fat-free mass, with little or no weight loss
SARCOPENIA: involuntary loss of muscle mass
(Roubenoff R. et al, Amer. J. Clin. Nutr. 661: 192-6; 1997)
PRINCIPAL CAUSES OF WEIGHT LOSS IN
AGING (according MORLEY)
1) Social
2) Psychological
3) Medical
4) Age-related
SOCIAL CAUSES OF WEIGHT LOSS IN
ELDERLY SUBJECTS
Poverty
Social segregation
Shopping and cooking problems
In institutionalized subjects:
- different dietary habit
- monotony of meals
- problems in eating together with demented patients
or subjects with handicaps
PSYCHOLOGICAL CAUSES OF WEIGHT
LOSS IN ELDERLY SUBJECTS
 Bereavements
 Loneliness or feeling of abandonment
 Rejection for a too sad life and wish for death
 Depression
 Dementia
 Tardive anorexia nervosa
DRUG INFLUENCES ON NUTRITION
MODIFICATION OF
APPETITE
REDUCTION: Antibiotics, Penicillamine, non
steroidal antininflammatorys, laxatives,
levodopa, fenformine, cardiokinetics
INCREASE: gastrokinetic hormones,
sulphonylureas, neeuroleptics
REDUCTION OF
INTESTINAL
ABSORPTION
Antibiotics, barbiturates, cytostatics, non
steroidal antininflammatorys, colchicine,
corticosteroids, laxatives
ALTERATIONS OF
METABOLISM
Sympathomimetics increase the caloric
requirement
CHANGES IN
NUTRIENTS
EXCRETION
Isoniazid e Penicillamine (increased vit. B12
excretion)
Colestiramine → loss of liposoluble vitamins
THE MEALS-ON-WHEELS APPROACH TO WEIGHT LOSS
M
E
A
L
S
=
=
=
=
=
Medication
Emotional (depression, late life mania)
Anorexia Nervosa (tardive); Alcoholism
Late life paranoia
Swallowing disorders
O = Oral factors (dental problema; xerostomia)
N = No Money (poverty)
W
H
E
E
L
S
=
=
=
=
=
=
Wandering and other dementia related behaviors
Hyperthyroidism; hyperparathyroidism
Entry problems (malabsorbtion)
Eating problems
Low salt; low cholesterol diet
Shopping problems
(J.F. MORLEY et al. PV 1992)
MALNUTRITION IN THE ELDERLY
•
5-10% of elderly people living at home
•
25-60% of elderly people living in a
nursing home
•
50% of hospitalized elderly subjects
GERONT.GERIATR., PV, 1995
PROTEIN-ENERGY MALNUTRITION IN
OLDER PERSONS
S: sadness
C: cholesterol < 4.14 mmol/l
A: albumin < 4 g/dl
L: loss of weight
E: eating problems
S: shopping problems or inhability to prepare meals
From Morley, Am J Clin Nutr, 1997:66:760
PROTEIN-ENERGY MALNUTRITION IN
OLDER PERSONS
Conditions associated with protein-energy
-Immunodeficiency (decreased helper T cells; increased
infection
-Pressure ulcers
-Anemia
-Osteopenia and sarcopenia
-Falls
-Cognitive deficits
-Altered drug metabolism
-Euthyroid sick syndrome
-Decreased maximal breathing capacity
-Decreased wound healing
From Morley, Am J Clin Nutr, 1997:66:760